For therapeutic treatment of diabetes mellitus, insulin preparations as injections or preparations of biguanide such as metformin hydrochloride or sulfonylurea such as tolbutamide as oral preparations have been conventionally used. However, the insulin preparations are inconvenient upon use as injections, whilst the biguanide preparations as oral preparations cause lactic acidosis and the sulfonylurea preparations have an adverse effect of severe hypoglycemia. Recently, thiazolidine-2,4-dione derivatives such as troglitazone (European Patent No. 139421), pioglitazone (European Patent No. 193256) and rosiglitazone (U.S. Pat. No. 5,002,953) have been focused, which are based on a novel mode of action of improvement of incompetence of insulin (insulin resistance) and free from the aforementioned adverse effects. However, troglitazone, pioglitazone and rosiglitazone have been reported to have side effects such as weight gain and edema, and troglitazone also has considerable problems, such as commercial distribution thereof has been discontinued due to high liver toxicity (J. Med. Chem., 35, 2617–2626, 1992). For these reasons, several thiazolidine-2,4-dione derivatives have been reported as described in Japanese Patent Unexamined Publication (Kokai) Nos. 10-139768 and 9-100280. However, no satisfactory therapeutic agent for insulin resistant diabetes mellitus is available at present.
Hyperlipidemia is a state of higher blood levels of triglyceride, cholesterol and the like than normal levels, and considered as an object of therapeutic treatment because the disease is a major risk factor of ischemic diseases. As hyperlipidemia is known to cause atherosclerosis, reduction of blood cholesterol level and/or blood triglyceride level is particularly effective for prophylaxis and treatment of atherosclerosis. Atherosclerosis is also known as a cause of myocardial infarction, cerebral thrombosis, peripheral artery obstruction, and atherosclerosis obliterans (Nippon Rinsho, Hyperlipidemia (First volume), 529–629, 2001).
As therapeutic agents for hyperlipidemia, fibrate-type drugs (for example, clofibrate, fenofibrate, bezafibrate) and statin-type drugs have been widely used. However, the fibrate-type drugs have insufficient cholesterol reducing effect, and the statin-type drugs have insufficient triglyceride decreasing effect. Moreover, the fibrate-type drugs are reported to have various side effects such as gastrointesitinal disorder, eruptions, headache, liver function failure, renal function failure, and biliary calculus. Furthermore, as the side effects of the statin-type drugs, rhabdomyolysis, myopathy, liver function failure, diarrhea, constipation and the like have been reported, and among them, rhabdomyolysis has been particularly problematic (Clin. Pharm. Ther., 69, 340–345, 2001; Nuc. Med. Commun., 22, 575–578, 2001; Ann. Pharmacoth., 35, 908–917, 2001). For these reasons, no satisfactory therapeutic agent for hyperlipidemia is available at present.